The overall objective of this proposal is to devise unique processes for the oxidative coupling of fragments via C-C, C-O, and C-N bond formation by means of C-H activation chemistry. Catalyst libraries will be designed for study of biomimetic reactions using the two guiding principles: 1) matching catalyst oxidation potentials with the oxidation potentials of the substrates under consideration and 2) selecting metals that can utilize oxygen to regenerate the catalytic species. These libraries will be deployed in a high-throughput microscale format to discover reactivity patterns heretofore unimagined in five areas: phenol coupling, aniline coupling, cross-coupling of enolic substrates with electron-rich aromatics, alkenyl phenol coupling, and other couplings/oxygenations. From the data obtained, reaction profiles will be constructed and new inferences about reactivity, selectivity, and mechanism will be made, which will be tested experimentally. The fundamental hallmark of this proposal is the ability to access new reaction patterns to construct important organic structures in an efficient and rational manner. High throughput microscale experimentation tools permit rational hypotheses to be interrogated broadly and facilitate optimization of the many interdependent variables in the possible reaction space. The development of new oxidative coupling chemistry leads to increases in efficiency due to lower step counts and smaller waste streams, because reaction sites no longer need to be preactivated with functional groups in order to obtain a selective reaction. As a consequence, the number of substrates for oxidative activation is intrinsically larger than for non-oxidative coupling processes. The challenge in this area follows from this fact, namely selectivity in any given transformation due the numerous C-H bonds present in a typical organic molecule. Use of biomimetic processes leads to bioactive natural products and natural product-like cores, desirable entities in medicinal chemistry. New synthetic methods greatly increase access to untapped chemical space, leading to materials and pharmaceuticals that benefit society. Invaluable training, absent outside of industrial settings, will be afforded to graduate students and other coworkers.